Reference to any prior art in this specification is not, and should not be taken as, an acknowledgement or any form of suggestion that this prior art forms part of the common general knowledge in Malaysia or any other country.
Shikimic Acid (SA) is an imperative biochemical intermediate in plants and microorganisms and has emerged as a vital starting material in the synthesis of an anti-influenza drug, widely known as Tamiflu (oseltamivir). It is discovered to be highly functionalized and it plays a major role in the production of essential aromatic amino acids which are not synthesized in the human body, such as phenylalanine, tryptophan and tyrosine. Presently, shikimic acid can be obtained based on microbe-catalyzed synthesis schemes or from plants, whereby the primary plant-based source for shikimic acid is the star anise (Illicium anisatum), whereby the yield of shikimic acid from star anise seed can be as high as 7%.
Oseltamivir, also known as the trade name Tamiflu, aids in the treatment and prophylaxis of both influenza virus A and influenza virus B infection, by way of blocking the influenza virus from spreading between cells and body. The administration of oseltamivir is preferably conducted within 48 hours from the first appearance of flu symptoms, as during this period it is observed that the virus has yet to replicate and infect many cells thus inhibition is considerably more effective. Under normal circumstances, the compound from Tamiflu is hydrolyzed by esterase in the liver, forming active form of drug, which is the oseltamivir carboxylate. Oseltamivir carboxylate then binds to and thereby inhibits viral neuraminidase. Such inhibition of neuraminidase by Tamiflu and other neuraminidase inhibitors prevents the release of new virus from the infected host cells.
It is observed based on current conditions that the primary challenge in oseltamivir production is the availability of a viable source of shikimic acid. As shikimic acid cannot be synthesized economically, the notion in shortage of shikimic acid has been surfaced due to increasing demand and consequently researchers began bioprospecting in many areas, in their endeavors to find alternative sources apart from star anise seed as briefly mentioned above. Accordingly, shikimic acid content has been discovered in a number of plants, particularly in the seeds of the sweetgum fruit, the Indian plant Calophylium apetalum and Araucaria excelsea. Nevertheless, it has been observed that these plants produce toxic compounds that necessitate prohibitively expensive refinement methods to ensure and thus obtain purified shikimic acid.
It is being reported that at least 50 million people have been treated with oseltamivir and this amount is expected to increase within the upcoming years. It is further estimated that the market size for Tamiflu will be at 400 million doses per year, at which 130 mg of shikimic acid is required to synthesize one dose of Tamiflu. From here, it can be expected that at least 52 metric tons of shikimic acid is required to meet the upcoming demands. Although production can be increased by way of replacing isolation from plant sources with recombinant microbial catalysts following the need but shortage of shikimic acid will intermittently be a challenging factor especially in the occurrence of a pandemic worldwide.
Following this there is a great need to provide a renewable and inexpensive source or viable alternative sources of shikimic acid.
The commercial value of oil palm (Elates guineensis) is in the oil, which offers various health advantages and benefits, owing to its high content of phytonutrients demonstrate antioxidant properties. Nevertheless, at present, the oil palm-based extracts, in particular its vegetation liquour and palm oil mill effluent (POME), has been discovered by way of various studies to have beneficial implications on skin ageing, cancer and heart diseases.
Malaysia is currently one of the world's largest producers of palm oil. Being the major foreign exchange earner industry and to fulfill the rapid progression of the world's demand for palm oil based on the world population growth, Malaysia has at least 265 palm oil mills all over the country.
Typically, the extraction of palm oil which is the primary product of palm fruit, involves a combination of various processes, wherein the main steps include the reception of fresh fruit bunches from plantations, sterilizing and threshing of the bunches, mashing the fruit and pressing the crude palm oil prior to storage and exportation. However, the extraction of palm oil leads to the production of oil palm vegetation liquor which is discarded in the waste stream as Palm Oil Mill Effluent (POME). In addition, Empty Fruit Bunches (EFB) and other waste materials are discarded in the milling process.
Palm oil mill effluent (POME) for instance, if untreated, is a pollutant due to the high chemical oxygen demand (COD) and biological oxygen demand (BOD). The major components of POME include oil and grease and solids, while elements found in POME include phosphorus, potassium, boron, iron, manganese, copper, magnesium and zinc. So far POME has been used in the preparation of fertilizers or as a substrate for bacterial production of biodegradable plastics.
It is being reported that more than 500 kg (around 0.5 m3) of liquid wastes, primarily in the form of palm oil mill effluent (POME), are discharged during the processing of 1.0 metric tons of fresh fruit bunches (Ma et al. 1996) in a typical oil palm mill. Accordingly, it is expected that more than 50 m3 of POME from a mill after processing 100 metric tons of fresh fruit bunches.
Proceeding from the above and based on recent studies on phytochemicals extracted from oil palm, the palm oil industry creates an abundance of prospect in beneficial phytochemicals and other compounds recovery due to the amount of oil palm-based materials including waste materials generated from the industry, if treated effectively.
It is a primary object of the present invention to provide a method for production of shikimic acid based on oil palm extracts.
It is yet another object of the present invention to provide a method for production of shikimic acid based on oil palm by-products.
It is another object of the present invention to provide a composition and a method for producing a composition comprising shikimic acid obtained from oil palm vegetation liquor.
It is yet another object of the present invention to provide a composition and a method for producing shikimic acid obtained from palm oil mill effluent (POME).
It is yet another object of the present invention to provide a composition comprising shikimic acid obtained from extracts from oil palm-based materials and method for producing said shikimic acid based on oil palm-based materials.
It is yet another object of the present invention to provide a composition comprising oil palm phenolics (OPP) with shikimic acid content and method for producing said shikimic acid based on oil palm-based materials.
It is yet a further object of the present invention to provide a composition and method for producing shikimic acid obtained from oil palm liquid waste-based materials.
Further objects and advantages of the present invention may become apparent upon referring to the preferred embodiments of the present invention as shown in the accompanying drawings and as described in the following description.